Mepolizumab治疗重症嗜酸性粒细胞哮喘的临床疗效和“超级反应者”的特征
2020/05/14
摘要
背景：Mepolizumab是首个获得许可的用于重症嗜酸性粒细胞性哮喘（SEA）的抗IL5单抗。迄今为止，几乎没有数据可以证实其在现实环境中或评估与反应相关的基线特征的功效。
方法：我们对英国区域性哮喘中心接受Mepolizumab（100mg sc）治疗SEA至少16周的所有患者进行了回顾性研究。在每4周一次的访问中收集临床数据。在第16、24和52周时，患者被分为“有反应者”或“无反应者”。有反应定义为急性加重下降≥50％，或需要维持口服皮质类固醇（mOCS）的患者泼尼松龙剂量减少≥50％。超级反应者定义为一年内无加重和停用mOCS。
结果：99例患者纳入分析。1年后哮喘急性加重从基线4.04（2.57）降低到1.86（2.17）（降低54％，p <0.001）。开始使用Mepolizumab时，有68名受试者接受了mOCS治疗。一年时间每日平均剂量从10mg（IQR 10-15）降至0mg（IQR 0-10，p <0.001）。57％的患者能够终止mOCS。72.7％（95％CI 63.0-80.7）的患者被分为反应者，28.3％（95％CI 20.2-38.0）被分为超级反应者。与反应者和超级反应者状态相关的基线特征包括：鼻息肉（p = 0.012），较低的ACQ6（p = 0.006），较低的BMI（p = 0.014）以及在mOCS患者中较低的泼尼松龙剂量（p = 0.005）。在第16周时，80.8％的患者识别了1年反应者状态，到24周时这一比例上升到92.9％。
结论：在现实世界的SEA队列中，Mepolizumab治疗可降低加重频率和mOCS需求。基线时鼻息肉、较低的BMI和较低的泼尼松龙维持剂量与较好的预后相关。到第24周时，超过90％的患者可确定12个月的反应。
Real-World Effectiveness and the Characteristics of a 'Super-Responder' to Mepolizumab in Severe Eosinophilic Asthma.
Joanne E Kavanagh, G d'Ancona, M Elstad, L Green, M Fernandes, C Roxas, J Dhariwal, A M Nanzer, B D Kent, D J Jackson.
Abstract
BACKGROUND:Mepolizumab was the first licensed anti-IL5 mAb for severe eosinophilic asthma (SEA). To date there is little data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response.
METHODS:We conducted a retrospective review of all patients who received at least 16 weeks of treatment with mepolizumab (100mg sc) for SEA at our regional asthma centre in the UK. Clinical data was collected at each 4-weekly visit. At 16, 24 and 52 weeks, patients were classified as 'responders' or 'non-responders'. A response was defined as ≥50% reduction in exacerbations, or for patients requiring maintenance oral corticosteroids (mOCS), ≥50% reduction in prednisolone dose. Super-responders were defined as exacerbation-free and off mOCS at one year.
RESULTS:99 patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04(2.57) to 1.86(2.17) at 1 year (54% reduction, p<0.001). 68 subjects were on mOCS at the time of commencing mepolizumab. By one year the daily median dose fell from 10mg (IQR 10-15) to 0mg (IQR 0-10, p<0.001). 57% were able to discontinue mOCS. 72.7% (95%CI 63.0-80.7) patients were classified as responders and 28.3% (95%CI 20.2-38.0) as super-responders. Baseline characteristics associated with responder and super-responder status included: the presence of nasal polyposis (p=0.012), lower baseline ACQ6 (p=0.006), a lower BMI (p=0.014), and in those on mOCS a significantly lower prednisolone dose at baseline (p=0.005). At 16 weeks, the 1-year responder status was correctly identified in 80.8% patients and by 24 weeks this rose to 92.9%.
CONCLUSIONS:In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in over 90% of patients by week 24.
背景：Mepolizumab是首个获得许可的用于重症嗜酸性粒细胞性哮喘（SEA）的抗IL5单抗。迄今为止，几乎没有数据可以证实其在现实环境中或评估与反应相关的基线特征的功效。
方法：我们对英国区域性哮喘中心接受Mepolizumab（100mg sc）治疗SEA至少16周的所有患者进行了回顾性研究。在每4周一次的访问中收集临床数据。在第16、24和52周时，患者被分为“有反应者”或“无反应者”。有反应定义为急性加重下降≥50％，或需要维持口服皮质类固醇（mOCS）的患者泼尼松龙剂量减少≥50％。超级反应者定义为一年内无加重和停用mOCS。
结果：99例患者纳入分析。1年后哮喘急性加重从基线4.04（2.57）降低到1.86（2.17）（降低54％，p <0.001）。开始使用Mepolizumab时，有68名受试者接受了mOCS治疗。一年时间每日平均剂量从10mg（IQR 10-15）降至0mg（IQR 0-10，p <0.001）。57％的患者能够终止mOCS。72.7％（95％CI 63.0-80.7）的患者被分为反应者，28.3％（95％CI 20.2-38.0）被分为超级反应者。与反应者和超级反应者状态相关的基线特征包括：鼻息肉（p = 0.012），较低的ACQ6（p = 0.006），较低的BMI（p = 0.014）以及在mOCS患者中较低的泼尼松龙剂量（p = 0.005）。在第16周时，80.8％的患者识别了1年反应者状态，到24周时这一比例上升到92.9％。
结论：在现实世界的SEA队列中，Mepolizumab治疗可降低加重频率和mOCS需求。基线时鼻息肉、较低的BMI和较低的泼尼松龙维持剂量与较好的预后相关。到第24周时，超过90％的患者可确定12个月的反应。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校 )
(Chest. 2020 Apr 7; S0012-3692(20)30574-2.)
(Chest. 2020 Apr 7; S0012-3692(20)30574-2.)
Real-World Effectiveness and the Characteristics of a 'Super-Responder' to Mepolizumab in Severe Eosinophilic Asthma.
Joanne E Kavanagh, G d'Ancona, M Elstad, L Green, M Fernandes, C Roxas, J Dhariwal, A M Nanzer, B D Kent, D J Jackson.
Abstract
BACKGROUND:Mepolizumab was the first licensed anti-IL5 mAb for severe eosinophilic asthma (SEA). To date there is little data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response.
METHODS:We conducted a retrospective review of all patients who received at least 16 weeks of treatment with mepolizumab (100mg sc) for SEA at our regional asthma centre in the UK. Clinical data was collected at each 4-weekly visit. At 16, 24 and 52 weeks, patients were classified as 'responders' or 'non-responders'. A response was defined as ≥50% reduction in exacerbations, or for patients requiring maintenance oral corticosteroids (mOCS), ≥50% reduction in prednisolone dose. Super-responders were defined as exacerbation-free and off mOCS at one year.
RESULTS:99 patients were included in the analysis. Asthma exacerbations decreased from a baseline of 4.04(2.57) to 1.86(2.17) at 1 year (54% reduction, p<0.001). 68 subjects were on mOCS at the time of commencing mepolizumab. By one year the daily median dose fell from 10mg (IQR 10-15) to 0mg (IQR 0-10, p<0.001). 57% were able to discontinue mOCS. 72.7% (95%CI 63.0-80.7) patients were classified as responders and 28.3% (95%CI 20.2-38.0) as super-responders. Baseline characteristics associated with responder and super-responder status included: the presence of nasal polyposis (p=0.012), lower baseline ACQ6 (p=0.006), a lower BMI (p=0.014), and in those on mOCS a significantly lower prednisolone dose at baseline (p=0.005). At 16 weeks, the 1-year responder status was correctly identified in 80.8% patients and by 24 weeks this rose to 92.9%.
CONCLUSIONS:In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in over 90% of patients by week 24.
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泼尼松龙/皮质醇测定在重症哮喘患者中维持口服泼尼松龙依从性的研究及临床应用
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法国、德国、意大利和英国的哮喘患者口服皮质类固醇处方模式
